Our major objective continues to be a search for methods which, in a rat preparation permitting simultaneous infusion and blood sampling, can reverse the effects of fatty acidemia induced by intravenous infusion of sodium salts of short and long chain fatty acids. A colony of double cannulated rats has been maintained on a diet deficient in lysine and carnitine in an attempt to sensitize the animals to the effects of long chain fatty acidemia. A major complication encountered has been the fatty acid dose related hemolysis which can lead to severe anemia accompanied by fatal renal and pulmonary effects. The use of a medium chain length fatty acid (e.g., octanoic) has overcome the severe anemia resultant with long chain fatty acids (e.g., oleic) and permits a separation of the pharmacologic action of the fatty acids from their physiological actions. The effects of octanoate infusion on hepatic lipid metabolism in rats which have fatty livers due to orotic acid containing diets (1%), has been followed by the use of radioactive fatty acids (palmitic-1 or 16-14C; linoleic-1-14C). The fatty acidemia in such animals results in accelerated hepatic synthesis of neutral lipid, sharply depressed phosphatidylcholine synthesis, and severely impaired ability of the liver to secrete Very Low Density Lipo-proteins.